Table 1.
Shared mechanistic role of senescent T cells in glomerulonephritis and atherosclerosis
| Senescent CD4+ and/or CD8+ lymphocytes | Glomerulonephritis | Atherosclerosis (CD4+ ≥ CD8+) | References |
|---|---|---|---|
| Increased cytokine production (IFN‐γ, TNF‐α) | Glomerular and interstitial damage | Development of atherosclerosis | 6, 38, 56, 60 |
| Endothelial toxicity (granzyme/perforin) | Glomerular endothelial cell lysis (CD4) | Endothelial damage‐ plaque rupture (CD4) | 6, 13, 24, 74 |
| Activation of macrophages and monocytes | Glomerular and interstitial damage (CD4/CD8) | Development of atherosclerosis (CD4 > 8) | 6, 41, 43, 48, 49, 50, 59 |
| Oxidative‐stress dependent activation of β2 integrin (LFA‐1) | Binding on ICAM‐1 on renal epithelial, mesangial, and endothelial cells | Binding on ICAM‐1 on endothelial cells and promotion of plaque destabilisation | 3, 17, 18 |
| Increased expression of CX3CR1 | The CX3CR1/fractalkine axis promotes glomerulonephritis | The CX3CR1/fractalkine axis promotes atherosclerosis | 16, 66, 67, 70, 114 |
| Enhancement of activation and proliferation by IL‐15 | IL‐15 promotes glomerulonephritis | IL‐15 promotes atherosclerosis in conjunction with fractalkine | 11, 12 |
| Triggered by HSP | HSP activate innate and adaptive immunity in glomerulonephritis | HSP play an active role in atherosclerosis | 9, 51, 115 |
| Higher plasma concentration with HLA DRB1*04 genotype | HLA DRB1*04 predisposes to SLE nephritis | HLA DRB1*04 predisposes to cardiovascular disease | 32, 33, 34 |
| Increased protease production (especially TEMRA) | Proteases (MMP) promote glomerulonephritis | Active role proteases (MMP) in development and progression of atherosclerosis | 2, 116 |
HSP, heat‐shock protein; ICAM‐1, Intercellular Adhesion Molecule 1; IFN‐γ, interferon‐gamma; IL‐15, interleukin‐15; LFA‐1, Lymphocyte function‐associated antigen 1; MMP, matrix metalloproteinase; TNF‐α, tumor‐necrosis factor alpha.